Zoltan Hajos

Zoltan Hajos
Born 3 March 1926
Budapest, Hungary
Nationality Hungarian, American
Fields Organic chemistry
Institutions Hoffmann-La Roche, Johnson & Johnson
Alma mater Technical University of Budapest
Doctoral advisor Zoltan Csuros
Known for Organocatalysis, total synthesis of steroids

Zoltan Hajos (born 3 March 1926) is a Hungarian born American organic chemist.

Biography

Zoltan Hajos studied chemistry at the Technical University of Budapest, Hungary (TU Budapest). He graduated in 1947 with an M.Sc. He received a Certificate of Merit, an Iron Award from the Technical University on May 22, 2013 in recognition of Sixty Five years of professional service. He finished his doctoral thesis work from 1947 to 1950. His advisor was Professor Zoltan Csuros of the Institute of Organic Chemical Technology. Hajos was thereafter Assistant Professor and lecturer of organic chemistry at the TU Budapest (1948 – 1952) and the University of Veszprem (1952 – 1953), thereafter Research Associate at the Institute of Organic Chemistry at the TU Budapest (1953-1956). After the Freedom fight of 1956 has been stricken down Hajos left his country, escaped to the USA, where he worked as Research Associate for Organic Chemistry at the Department of Chemistry, Princeton University, Princeton, NJ (1957 – 1960). Hajos was from 1960 to 1970 a chemist at the Pharmaceutical Research Institute of Hoffmann-La Roche, Inc., Nutley, NJ (USA). He was then Research Associate at the Chemistry Department of the University of Vermont, USA (1972 -1973), and thereafter at the Faculty of Pharmacy of the University of Toronto, Canada (1973 -1974). Hajos has worked from 1975 until 1990 in distinguished positions at the Research Institute of Johnson & Johnson, the USA based large pharmaceutical company.

Research

Zoltan Hajos became especially noted through the discovery of the Hajos–Parrish–Eder–Sauer–Wiechert reaction named after him, and through the related (S)-proline catalyzed synthesis of the Hajos-Wiechert-Ketone.[1] The solvent free green chemistry version of “The Hajos-Parrish Cyclisation” has been highlighted in 1996 by Professors Andrew B. Holmes and G. Richard Stephenson in Chemistry & Industry.[2] The solvent free green procedure was originally described in a U.S. Patent filed in 1970.[3]

Zoltan Hajos thus belongs to the pioneers of the research area of Organocatalysis.The last few lines of the Hajos and Parrish 1974 paper read: "We believe our results may be considered an example of a simplified model of a biological system in which (S)-(–)-proline plays the role of an enzyme." This has been referred to in a publication by Mohammad Movassaghi and Eric N. Jacobsen of the Department of Chemistry and Chemical Biology, Harvard University.[4] Also in 2002 molecular biology professor Carlos F. Barbas III and coworkers at Scripps Research Institute reported proline-catalyzed asymmetric Mannich reactions in which underivatized aldehydes are used for the first time as a source of nucleophiles.[5] In the Science & Technology report of Chemical & Engineering News Barbas referred to the work in the 1970s on proline-catalyzed intramolecular aldol addition reactions by synthetic organic chemists Zoltan G. Hajos and David R. Parrish of the chemical research department at Hoffmann-La Roche, Nutley, N.J., which "inspired us to look more closely at parallels between small-molecule catalysis and enzymes." [6] According to a later issue of Chemical and Engineering News " the reactions' mechanics were ill defined, and they therefore had been widely viewed as exotic exceptions to the prevailing dogma that only enzymes and metal complexes can act as highly enantioselective, synthetically useful catalysts."[7] The scientific and practical results of the Hajos and Parrish intramolecular asymmetric aldol reactions have been confirmed by three independent researchers.[8]

Hajos and Parrish proposed two reaction mechanisms [ an enamine and a carbinolamine (imine) ]. Of these the enamine mechanism became more widely accepted.[9] The experimental results of the Hajos and Parrish laboratory with 18 O labeled water suggested the imine mechanism to be the more likely.[10] Therefore, the statement that the ”reactions’ mechanics were ill defined” should be reconsidered in this context.

Another Chemical and Engineering News item refers to the work of Keene P. Dimick whose team elucidated the key compound of strawberry flavor, 4-hydroxy-2,5-dimethyl-3(2H)-furanone.[11] The parent substance, Tetrahydro-3,4-furandione was synthesized by Edward C. Kendall and Zoltan G. Hajos at Princeton University.[12] The compound exists in the dione form with no evidence of enolization. The compound readily formed the dihydrate, 3,3,4,4-tetrahydrofurantetrol whose crystal structure was determined by Alan D. Mighell and Robert A Jacobson at Princeton University.[13] In Medicinal Chemistry the pioneering discoveries of Hajos created the basis of the development of stereospecific total synthesis of steroids.[14] His research led to the discovery of Carsatrin a 6-mercaptopurine derivative of potential cardiac active use.[15]

Publications and Patents

The research activity of Zoltan Hajos resulted in about 45 scientific publications in technical journals as well as in more than 30 patents.

Selected Publications

References

  1. ↑ Takashi Nagamine, Kohei Inomata, Yasuyuki Endo und Leo A. Paquette: Amino acid mediated intramolecular asymmetric aldol reaction to construct a new chiral bicyclic enedione containing a seven-membered ring: Remarkable inversion of enantioselectivity compared to the six-membered ring example, Journal of Organic Chemistry 72 (2007) 123−131.
  2. ↑ Andrew B. Holmes and G. Richard Stephenson, “Highlights” in Chemistry and Industry, 16 September, 1996, 693-694.
  3. ↑ Example 4 in U.S. Patent 3,975,440 August 17, 1976, Filed Dec. 9, 1970 Zoltan G. Hajos and David R. Parrish.
  4. ↑ The Simplest "Enzyme" Science, 6 December 2002, Vol. 298, 1904-1905.
  5. ↑ J. Am. Chem. Soc., 2002, 1866.
  6. ↑ Stu Borman, Improving Classics, Chemical & Engineering News, February 25, 2002, p.33.
  7. ↑ Jean-François Tremblay: Benjamin List, Chemical & Engineering News, March 17, 2014, p. 49.
  8. ↑ Organic Syntheses, Coll. Vol. 7, 363
  9. ↑ Wiener, J.J.M. Amer. Chem. Soc., Div. of Org. Chem. 2001 Fellowship Award Essay “Enantioselective Catalysis by Simple Chiral Amines: The Search for a General Strategy”
  10. ↑ J. Org. Chem. 1974, 39, 1615-1621
  11. ↑ Elizabeth K. Wilson: USDA Lab Named Landmark, Chemical & Engineering News, April 28, 2014, p. 32.
  12. ↑ J. Am. Chem. Soc., 1960, 82 (12), 3219-3220.
  13. ↑ Acta Cryst. (1964), 17, 1554 - 1560.
  14. ↑ R. A. Micheli, Z. G. Hajos, N. Cohen, D. R. Parrish, L. A. Portland, W. Sciamanna , M. A. Scott, P. A. Wehrli: Total Synthses of optically-active 19-Norsteroids - (+)-Estr-4-ene-3,17-dione and (+)-13β-ethylgon-4-ene-3,17-dione, Journal of Organic Chemistry 40 (1975) 675−681.
  15. ↑ Synthesis and SAR of 6 substituted purine derivatives, Journal of Medicinal Chemistry 35 (1992) 4509-4515.